The ecology of mammalian intestinal flora remains one of the poorly understood fields in microbiology. Because of the technical difficulties involved, most current studies are still of a descriptive nature, attempting to identify the various microbial species and their distribution throughout the numerous macroscopic and microscopic habitats which together comprise the intestinal tract. The present proposed study will by necessity have to include a certain amount of preliminary work of such descriptive nature. However, the main purpose of the proposed work is to go one step further and to study the ecologic control mechanisms operating in the intestine. Among the mechanisms to be studied are (1) those which cause the composition of the enteric flora to be stable, and (2) those which enable the enteric flora to suppress the growth of enteric pathogens. In contrast to earlier work from the writer's laboratory which was concerned with the in vivo interactions between single strains in a simplified "normal" flora, the present project is to study the entire, intact normal flora. Special consideration will be given to a study of the role played by the predominant gram negative anaerobes for which special culture methods have been devised. Populations of "normal" bacterial enteric flora have been synthesized by introducing pure bacterial cultures, originally isolated from conventional mice, into germfree mice. These populations change the germfree characteristics of the animals to those found in conventional mice. In vitro models such as continuous flow cultures will be devised in which bacterial interactions observed in the intestine can be duplicated. Mechanisms of interaction between the bacteria will then be studied biochemically in the in vitro model system.